OSCR

A<sub>3</sub> adenosine receptor regulates depression-like behaviors through astrocyte-nourished excitatory synapse formation.

Overview

Authors: Bai Li1, Meng Zeng1, Jiahui Liu1, Wanqing Huang1, Dan Pan1, Chunjie Xiao1, Jing Du1,2
ORCID iDs: Bai Li, Jing Du
  1. School of Medicine, Yunnan University, Kunming, Yunnan 650091, China
  2. The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China
Institutions: Yunnan University (China); Capital Medical University (China); Beijing Anding Hospital (China)
Journal: iScience, volume 29, issue 8, article 116843
Dates: received 27 June 2025; accepted 2 July 2026; published online 16 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.116843 · PMID 42502380 · PMCID PMC13401021 · OpenAlex W7168917174
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: mouse (organism), depression (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: major depressive disorder, A3 adenosine receptor, neuroligin-2, astrocyte, Synaptogensis
Topic: Adenosine and Purinergic Signaling (Physiology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Natural Science Foundation of China (National Science Foundation of China) (81960657); Science and Technology Innovation Fund of China (2021ZD0202003); Science and Technology Project of Yunnan Province (202201AT070298); Yunnan Provincial Key Research and Development Plan (202403AC100020)
Citations: not cited yet (Europe PMC); 91 references in the paper
Research resources: pGluR1 Ser845 antibody RRID:AB_1523688, RRID:AB_228307, RRID:AB_228341, RRID:AB_2338840, RRID:AB_2340621, Tubulin antibody RRID:AB_2813772, BDNF antibody RRID:AB_2818984, GluR1 antibody RRID:AB_2835154, Rabbit IgG RRID:AB_2905533, Synapsin-1 antibody RRID:AB_2920663, PSD-95 antibody RRID:AB_298846, A3AR antibody RRID:AB_3751512, GFAP antibody RRID:AB_3751513, NRXN2 antibody RRID:AB_776702, NLGN2 antibody RRID:AB_993014

Abstract

Abnormal excitatory synaptic function plays a critical role in major depressive disorder. In this study, we investigated the role of the A3 adenosine receptor (A3AR), previously implicated in affective disorders, in excitatory synapse formation within prefrontal cortical circuits. Using a corticosterone-induced mouse model of depression, we found that the adenosine receptor activator 3′-deoxyadenosine (3′dA) produced antidepressant-like effects and selectively increased A3AR expression, whereas fluoxetine did not. 3′dA also restored the synaptic organizers neuroligin-2 (NLGN2) and neurexin-2 and elevated BDNF, excitatory synaptic markers (synapsin-1, PSD-95, and GluR1), and dendritic spine density in the PFC. Notably, enhanced NLGN2 immunoreactivity co-localized with astrocytes exclusively in 3′dA-treated mice but not in fluoxetine-treated mice. Pharmacological blockade of A3AR with MRS-1191 prevented the 3′dA-induced behavioral and molecular changes in this corticosterone-induced depressive-like mouse model. Together, our findings identify A3AR as a key regulator of NLGN2 expression and excitatory synapse formation and suggest a potential target for antidepressant therapies.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

No dataset and no data link were found in the paper.

Data and code availability

• All data supporting the findings of this study are available from the lead contact upon reasonable request. • This study does not report any original code. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 5 keywords, 4 funders, 91 references, 15 RRIDs.

Cite

This paper

Li, B., Zeng, M., Liu, J., Huang, W., Pan, D., Xiao, C., & Du, J. (2026). A<sub>3</sub> adenosine receptor regulates depression-like behaviors through astrocyte-nourished excitatory synapse formation. iScience, 29(8), 116843. https://doi.org/10.1016/j.isci.2026.116843

BibTeX

@article{li2026lt,
author = {Li, Bai and Zeng, Meng and Liu, Jiahui and Huang, Wanqing and Pan, Dan and Xiao, Chunjie and Du, Jing},
title = {{A\<sub\>3\</sub\> adenosine receptor regulates depression-like behaviors through astrocyte-nourished excitatory synapse formation}},
journal = {iScience},
year = {2026},
month = jul,
volume = {29},
number = {8},
pages = {116843},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.116843},
url = {https://doi.org/10.1016/j.isci.2026.116843},
pmid = {42502380},
pmcid = {PMC13401021}
}

RIS

TY - JOUR
AU - Li, Bai
AU - Zeng, Meng
AU - Liu, Jiahui
AU - Huang, Wanqing
AU - Pan, Dan
AU - Xiao, Chunjie
AU - Du, Jing
TI - A<sub>3</sub> adenosine receptor regulates depression-like behaviors through astrocyte-nourished excitatory synapse formation
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/07/16
VL - 29
IS - 8
SP - 116843
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.116843
UR - https://doi.org/10.1016/j.isci.2026.116843
LA - en
ER -

CSL-JSON

{
"id": "10.1016/j.isci.2026.116843",
"type": "article-journal",
"title": "A<sub>3</sub> adenosine receptor regulates depression-like behaviors through astrocyte-nourished excitatory synapse formation",
"container-title": "iScience",
"author": [
{
"family": "Li",
"given": "Bai"
},
{
"family": "Zeng",
"given": "Meng"
},
{
"family": "Liu",
"given": "Jiahui"
},
{
"family": "Huang",
"given": "Wanqing"
},
{
"family": "Pan",
"given": "Dan"
},
{
"family": "Xiao",
"given": "Chunjie"
},
{
"family": "Du",
"given": "Jing"
}
],
"container-title-short": "iScience",
"volume": "29",
"issue": "8",
"page": "116843",
"DOI": "10.1016/j.isci.2026.116843",
"PMID": "42502380",
"PMCID": "PMC13401021",
"ISSN": "2589-0042",
"publisher": "Elsevier",
"URL": "https://doi.org/10.1016/j.isci.2026.116843",
"language": "en",
"issued": {
"date-parts": [
[
2026,
7,
16
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1111/ejn.70665
Baseline Dynamics and Sleep Loss-Driven Changes of Electrocorticographic Aperiodic Properties Are Altered in Mice Lacking Neuroligin-2.
Journal: The European journal of neuroscience
In common: mouse, cellular / molecular, 4 references
[2] doi:10.1523/eneuro.0471-25.2026 [code]
Attack Repertoires in Outbred Male CD1-Mice Are Associated with Nucleus Accumbens Neuroligin-2.
Journal: eNeuro
In common: mouse, cellular / molecular, 3 references
[3] doi:10.3390/antiox15070908 [code]
Convergent Lower Expression of Redox-Linked Stress-Adaptation and Synaptic-Plasticity Genes in Major Depressive Disorder Across Seven Postmortem dlPFC Cohorts.
Journal: Antioxidants (Basel, Switzerland)
In common: depression, cellular / molecular, 3 references
[4] doi:10.1038/s41467-026-71542-5 [code]
Astrocyte fatty acid metabolism as a driver of risk for major depressive disorder.
Journal: Nature communications
In common: depression, cellular / molecular, 2 references
[5] doi:10.1111/jnc.70502 [code]
The Converging Effects of Different Categories of Antidepressants on the Brain: A Systematic Meta-Analysis of Public Transcriptional Profiling Data From the Hippocampus and Cortex.
Journal: Journal of neurochemistry
In common: depression, mouse, cellular / molecular, 2 references
[6] doi:10.1038/s41467-026-77377-4 [code]
Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization.
Journal: Nature communications
In common: mouse, cellular / molecular, 2 references
[7] doi:10.1001/jamanetworkopen.2026.33507 [code]
Illness Severity and Longitudinal Gray Matter Volumes Among People With Major Depressive Disorder.
Journal: JAMA network open
In common: depression, 2 references
[8] doi:10.1111/pcn.70066
Acute prefrontal hemodynamic responses to intermittent theta burst stimulation correlate with current depression and episode recurrence: A cross-sectional study.
Journal: Psychiatry and clinical neurosciences
In common: depression, 2 references
[9] doi:10.1038/s41467-026-77248-y [code]
The mPFC-reuniens-hippocampus pathway links brain circuitry and neural plasticity in antidepressant response.
Journal: Nature communications
In common: depression, mouse, 2 references
[10] doi:10.1073/pnas.2601657123 [code]
Mitofusin-2 in ventral striatal D1 neurons regulates effort-based motivation through sex-specific mitochondrial-synaptic reprogramming.
Journal: Proceedings of the National Academy of Sciences of the United States of America
In common: mouse, cellular / molecular, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.